[Prevalence of Adverse Effects of Tyrosine Kinase Inhibitors Used in Management of Chronic Myeloid Leukemia at Sidi Bel-Abbès University Hospital Center]. / Prévalence des Effets Indésirables des Inhibiteurs de Tyrosine Kinase Utilisés dans le Traitement de la Leucémie Myéloïde Chronique au CHU de Sidi Bel-Abbès.

INTRODUCTION: Chronic myeloid leukemia (CML) is a malignant hemopathy within the framework of chronic myeloproliferative syndromes, predominant on the granular line. Her drug treatment is based on tyrosine kinase inhibitors (TKIs) which inhibit the abnormal BCR-ABL protein kinase that causes CML and thus block the signals that cause cancer cells to multiply abnormally. However, other proteins are also inhibited, so they can cause a wide range of adverse effects (AEs). The objective of this study was to study the prevalence of AEs of TKIs used in the therapeutic management of CML by the hematology department of University Hospital Center (UHC) of Sidi Bel-Abbes in Algeria and that of the ITK discontinuation following an AE. MATERIALS AND METHODS: It was a retrospective descriptive study carried out over a period of four months, from April 01st, 2021 to July 31st, 2021, on CML patients treated with TKI in the hematology department of Sidi Bel-Abbes HUC in Algeria. The primary outcome measure was the prevalence of AEs associated with the use of normal dosages or overdose of the following TKIs: Imatinib, Dasatinib and Nilotinib. Data were collected from patient charts, filled by doctors of hematology department, using questionnaire, and analyzed by Statistical Package for the Social Sciences software, version 20. RESULTS: A total of 40 patients were included, including 22 women, mean age 51.55±11.66years (23-78). Twenty-six patients reported at least one AE. Among the 106 AEs declared, 69 AEs (65.09 %) declared with Imatinib, 26 AEs (24.53 %) with Dasatinib and 11 AEs (10.38 %) with Nilotinib. A predominance of musculoskeletal effects 43 (40.56 %), followed by general disorders 18 (17 %), myelosuppression 14 (13.20 %) and digestive system 12 (11.32 %). AEs were responsible for permanent discontinuation of ITK in three cases (11.54 %), including two cases (07.70 %) on Imatinib because of neutropenia and one case (03.84 %) onDasatinibsuffering from pleural effusion. AEs could be controlled in 13 (50 %) of cases, including 9 (34.62%) by temporary discontinuation and 4 (15.38 %) by reducing the dosage, allowing improvement of symptoms and continuation or reintroduction of treatment. CONCLUSION: The prevalence of AEs was high in the studied population, their occurrence was inevitable, good management of AEs from the start of treatment is necessary to avoid switching to another TKI, especially in good responders. It is recommended to establish a low-sodium diet beforehand for all TKIs and a low-carbohydrate diet, especially for Nilotinib, and not to rush to stop the TKI because most often, EIs regress over time in order to allow good therapeutic adherence and obtain better results.

Quality of Active Pharmaceutical Ingredients Present on Algerian Soil: Control of Impurities of Ciprofloxacin, Metronidazole and Fluconazole.

INTRODUCTION: The medicine quality is defined by its aptitude to meet certain requirements declared by the regulatory authorities. Among these, impurities control which constitutes the major fear of pharmaceutical manufacturers in efficiency and safety terms. Nowadays, in many developing countries, the presence of poor quality drugs is common, for this reason, an increased control should be instituted including impurities which represent a serious public health problem threatening the efficacy and the safety medicines, because of their nocuous repercussions on health. The objective of this study is to verify that impurities in certain APIs: Ciprofloxacin, Metronidazole and Fluconazole actually collected on Algerian soil meet the impurity requirements. MATERIALS AND METHODS: An observational experimental study was carried out from 1st December 2013 to 31st December 2017, on impurities control in the APIs of Ciprofloxacin, Metronidazole and Fluconazole medicines registered in the Algerian Medicines Nomenclature and marketed in Algeria. All samples collected were analyzed to detect, quantify and evaluate impurties for rigorous control of three categories of impurties, such as: Organic related-impurities analysis by High-Pressure Liquid Chromatography with UV Detector (HPLC-UV), Elemental-impurities analysis by Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) and Residual Solvents-impurities analysis by Headspace Gas Chromatography with Flame Ionization Detection (HS-GC-FID). RESULTS AND DISCUSSION: 18 samples collected from 11 laboratories among 27 requested. 22% of non-conformities were detected, including 5.5% Indian origin, 5.5% Spanish origin, 5.5% French origin and 5.5% Chinese origin. These non-conformity cases are due to the high rate of degradation product-impurity for C5 sample, Cobalt-impurity and Nickel-impurity contents exceeding the required limits for C4 and M3 samples respectively, Methanol-impurity and Toluene-impurity contents exceeding the authorized limits for M2 and F3 samples respectively. CONCLUSION: This study concluded that samples non-compliance rate is high because of certain impurities detection exceeding the safety standards. So, we interpellate the health authorities to ensure the APIs impurities control before being put into the manufacturing process in order to prevent the potentially serious health problems that are difficult to control.

Outcomes of newborns to mothers with COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has spread rapidly across the world. Given the sharply increased infection rate, the number of pregnant women and children with COVID-19 is correspondingly on the rise. SARS-CoV-2 infection is transmitted through droplets; though hypothesized, other transmission routes have not been confirmed. As of now, it remains unclear whether and how SARS-CoV-2 can possibly be transmitted from the mother to the fetus. METHOD: This study examines the medical records of 30 neonates born to women with COVID-19, the objective being to provide documented information on maternal-child transmission and infant outcomes. RESULTS: Out of the 30 newborns, 28 had negative PCR test results for SARS-CoV-2; among their mothers, fifteen had fever, nine had cough and twenty had delivered by cesarean section. The median birth term was 37wk2dy, and twenty of the neonates were male. Most of them were asymptomatic, except for the three who presented with shortness of breath. Two of them were intubated and both died, the first because of severe sepsis and the second due to severe hyaline membrane disease. As regards the two infected neonates, the first represents a probable case of congenital SARS-CoV-2 infection, which appears unlikely in the second case. The outcome for both of them was good, without any complications. CONCLUSION: Maternal-fetal transmission of the SARS- CoV-2 virus was not detected in the majority of the reported cases, although two of 30 neonates had positive qRT-PCR test results. Our study supports the hypothesis that though it seldom actually occurs, in utero SARS-CoV-2 vertical transmission is possible.

Subchondral tibial bone texture predicts the incidence of radiographic knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVES: To evaluate whether trabecular bone texture (TBT) parameters measured on computed radiographs (CR) could predict the onset of radiographic knee osteoarthritis (OA). MATERIALS AND METHODS: Subjects from the Osteoarthritis Initiative (OAI) with no sign of radiographic OA at baseline were included. Cases that developed either a global radiographic OA defined by the Kellgren-Lawrence (KL) scale, a joint space narrowing (JSN) or tibial osteophytes (TOS) were compared with the controls with no changes after 48 months of follow-up. Baseline bilateral fixed flexion CR were analyzed using a fractal method to characterize the local variations. The prediction was explored using logistic regression models evaluated by the area under the receiver operating characteristic curves (AUC). RESULTS: From the 344 knees, 79 (23%) developed radiographic OA after 48 months, 44 (13%) developed progressive JSN and 59 (17%) developed osteophytes. Neither age, gender and BMI, nor their combination predicted poorer KL (AUC 0.57), JSN or TOS (AUC 0.59) scores. The inclusion of the TBT parameters in the models improved the global prediction results for KL (AUC 0.69), JSN (AUC 0.73) and TOS (AUC 0.71) scores. CONCLUSIONS: Several differences were found between the models predictive of three different outcomes (KL, JSN and TOS), indicating different underlying mechanisms. These results suggest that TBT parameters assessed when radiographic signs are not yet apparent on radiographs may be useful in predicting the onset of radiological tibiofemoral OA as well as identifying at-risk patients for future clinical trials.

Subchondral tibial bone texture analysis predicts knee osteoarthritis progression: data from the Osteoarthritis Initiative: Tibial bone texture & knee OA progression.

OBJECTIVES: To examine whether trabecular bone texture (TBT) parameters assessed on computed radiographs could predict knee osteoarthritis (OA) progression. METHODS: This study was performed using data from the Osteoarthritis Initiative (OAI). 1647 knees in 1124 patients had bilateral fixed flexion radiographs acquired 48 months apart. Images were semi-automatically segmented to extract a patchwork of regions of interest (ROI). A fractal texture analysis was performed using different methods. OA progression was defined as an increase in the joint space narrowing (JSN) over 48 months. The predictive ability of TBT was evaluated using logistic regression and receiver operating characteristic (ROC) curve. An optimization method for features selection was used to reduce the size of models and assess the impact of each ROI. RESULTS: Fractal dimensions (FD's) were predictive of the JSN progression for each method tested with an area under the ROC curve (AUC) up to 0.71. Baseline JSN grade was not correlated with TBT parameters (R < 0.21) but had the same predictive capacity (AUC 0.71). The most predictive model included the clinical covariates (age, gender, body mass index (BMI)), JSN and TBT parameters (AUC 0.77). From a statistical point of view we found higher differences in TBT parameters computed in medial ROI between progressors and non-progressors. However, the integration of TBT results from the whole patchwork including the lateral ROIs in the model provided the best predictive model. CONCLUSIONS: Our findings indicate that TBT parameters assessed in different locations in the joint provided a good predictive ability to detect knee OA progression.

Implications of the calf musculature and Achilles tendon architectures for understanding the site of injury.

UNLABELLED: Clinically the sites of Achilles Tendon (AT) overuse conditions can be divided into the tendon mid-portion and osteotendinous attachment. PURPOSE: We propose an anatomical analysis of the triceps surae musculotendon unit that could provide a possible anatomic explanation for these 2 sites of injury. METHOD: Twelve cadavers (age 74±7 years) were studied. In both legs, calf muscles (lateral gastrocnemius (LG), medial gastrocnemius (MG) and soleus) were dissected and their volumes measured. Fine saw cuts were made in the sagittal plane, either side of the midline of the calcaneus. Each strip contained the distal part of the tendon and its insertion, together with the superior tuberosity of the calcaneus. Trabecular architecture was analyzed from X-rays taken with Faxitron radiography. Histological sections of the enthesis and the thickness of the uncalcified fibrocartilage and the subchondral plate were evaluated. A finite element model of tendon coupled to a rupture index was developed to investigate the AT response to mechanical load. RESULTS: Muscle volume was highest for the soleus, followed by the MG, and LG. Within the AT, the soleus fibers occupy the antero-medial parts, the MG fibers form the posterior lateral layer, yet the LG head fibers retain the antero-lateral part. The quantity of bone and the apparent trabecular thickness at the enthesis were greatest in the central part of the enthesis. Thickness of calcified fibrocartilage tissue was significantly greater in the central part than medially (P=0.04) and laterally (P=0.03). Uncalcified fibrocartilage was significantly thicker medially than laterally (P=0.02). Finally, finite element analysis showed that AT mechanical stress increased with muscle load and converged at 4.6-7.9cm of the enthesis. CONCLUSION: Our data suggest that the triceps surae musculotendon unit is composed of anatomically distinct parts that undergo non-uniform mechanical loading. There are two sites where potentially tendon mechanical stress increases, the medial/central portions of the enthesis and the tendon midportion.

Fracture discrimination by combined bone mineral density (BMD) and microarchitectural texture analysis.

The use of bone mineral density (BMD) for fracture discrimination may be improved by considering bone microarchitecture. Texture parameters such as trabecular bone score (TBS) or mean Hurst parameter (H) could help to find women who are at high risk of fracture in the non-osteoporotic group. The purpose of this study was to combine BMD and microarchitectural texture parameters (spine TBS and calcaneus H) for the detection of osteoporotic fractures. Two hundred and fifty five women had a lumbar spine (LS), total hip (TH), and femoral neck (FN) DXA. Additionally, texture analyses were performed with TBS on spine DXA and with H on calcaneus radiographs. Seventy-nine women had prevalent fragility fractures. The association with fracture was evaluated by multivariate logistic regressions. The diagnostic value of each parameter alone and together was evaluated by odds ratios (OR). The area under curve (AUC) of the receiver operating characteristics (ROC) were assessed in models including BMD, H, and TBS. Women were also classified above and under the lowest tertile of H or TBS according to their BMD status. Women with prevalent fracture were older and had lower TBS, H, LS-BMD, and TH-BMD than women without fracture. Age-adjusted ORs were 1.66, 1.70, and 1.93 for LS, FN, and TH-BMD, respectively. Both TBS and H remained significantly associated with fracture after adjustment for age and TH-BMD: OR 2.07 [1.43; 3.05] and 1.47 [1.04; 2.11], respectively. The addition of texture parameters in the multivariate models didn't show a significant improvement of the ROC-AUC. However, women with normal or osteopenic BMD in the lowest range of TBS or H had significantly more fractures than women above the TBS or the H threshold. We have shown the potential interest of texture parameters such as TBS and H in addition to BMD to discriminate patients with or without osteoporotic fractures. However, their clinical added values should be evaluated relative to other risk factors.

Effects of anti-sclerostin antibody and running on bone remodeling and strength.

Sclerostin antibody (Scl-Ab) represents a promising therapeutic approach to treat patients with osteoporosis. PURPOSE: The aim of this study was to investigate the effects of Scl-Ab, running and a combination of both on bone formation. METHODS: Sixty female Wistar rats, aged 8 months were randomly assigned to five groups (subcutaneous injections performed twice a week): (1) (Sham): sedentary rats + saline, (2) (OVX): ovariectomized rats + saline, (3) (OVX + E): OVX rats + saline + treadmill training (5 times/week, 1 h/day), (4) (OVX + E + S): OVX rats + treadmill training + 5 mg/kg Scl-Ab and (5) (OVX + S): OVX rats + 5 mg/kg Scl-Ab. After 14 weeks, body composition, whole body and femoral BMDs were determined by DXA and serum was collected for analysis of osteocalcin and NTX. Bone microarchitecture was analyzed using µCT and bone strength was assessed at the femur mid-shaft in 3-point bending. RESULTS: Running exercise decreased fat mass as well as the bone resorption marker NTX relative to the non-exercised control groups, effects that were associated with a prevention of the deleterious effects of OVX on whole body and femoral BMDs. Scl-Ab increased the bone formation marker osteocalcin, which resulted in robust increases in BMD and femoral metaphyseal bone volume to levels greater than in the Sham group. OVX + S + E group did not further impact on bone mass relative to the OVX + S group. At the cortical femur diaphysis, Scl-Ab prevented the decreases in bone strength after OVX, while exercise did not affect cortical strength. CONCLUSION: We suggest that while running on a treadmill can prevent some bone loss through a modest antiresorptive effect, it did not contribute to the robust bone-forming effects of Scl-Ab when combined in an estrogen ablation model.

Mesenchymal stem-cell potential in cartilage repair: an update.

Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non-operative treatments endeavour to control symptoms and include anti-inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field.

Effect of interval-training exercise on subchondral bone in a chemically-induced osteoarthritis model.

OBJECTIVES: The role of subchondral bone in osteoarthritis (OA) development is well admitted. Cross-talk between subchondral bone and cartilage may be disrupted in OA, leading to altered subchondral bone remodeling. Osteocytes are involved in bone remodeling control and could play a key role in OA progression. Our purpose of this study was to evaluate the preventive effect of interval-training exercise on subchondral bone and osteocyte in monosodium iodoacetate (MIA) model of experimental OA. METHODS: At baseline, 48 male Wistar rats (8 weeks old) were separated into two groups: interval-training exercise or no exercise for 10 weeks. After this training period, each group was divided into two subgroups: MIA-injected knee (1 mg/100 µl saline) and saline-injected knee. Four weeks later, rats were sacrificed and carefully dissected. Evaluated parameters were: cartilage degeneration by OA scoring, bone mineral density (BMD) by Dual energy X-ray Absorptiometry (DXA), trabecular subchondral bone microarchitecture by micro-computed tomography (µCT), cortical subchondral bone lacunar osteocyte occupancy (by Toluidine Blue staining) and cleaved caspase-3 positive apoptosis (by epifluorescence). RESULTS: Our results showed deleterious effects of MIA on cartilage. OA induced a decrease in proximal tibia (PT) BMD which was prevented by exercise. Exercise induced increase in full osteocyte lacunae surface and osteocyte occupancy (+60%) of cortical subchondral bone independently of OA. Osteocyte apoptosis (<1%) in cortical subchondral bone was not different whatever the group at sacrifice. CONCLUSION: Our results suggest that preliminary interval-training improved BMD and osteocytes lacunar occupancy in subchondral bone. Our interval-training did not prevent MIA-induced cartilage degeneration.

Tibial subchondral bone mineral density: sources of variability and reproducibility.

OBJECTIVES: It has been shown that subchondral bone mineral density (sBMD) measurement may be a relevant parameter of osteoarthritis (OA) progression. However, factors implicating the reproducibility and contributing to the variability of the measurement have not been fully described. Thus, the aim of this study was to explore the reproducibility of sBMD by Dual energy X-ray Absorptiometry (DXA) and to further examine its sources of variability. METHODS: In this study, short-term, intra and inter-observer reproducibility of sBMD was examined on knee images obtained on DXA scans. The influence of software (lumbar spine and forearm modes), knee positioning (flexion or extension), site and size of regions of interest (ROI) and use of rice, on both lateral and medial tibial sBMD, were assessed. Root mean square coefficient of variation (RMS CV) and least significant changes (LSC) were calculated. RESULTS: The short-term precision of sBMD ranged between 2.24% and 5.12% for RMS CV and between 0.053 and 0.135 g/cm(2) for LSC. Good intra-observer precision was found for knee flexion conditions whatever the software used (RMS CV ranging from 0.43 to 1.41%). The reproducibility was dependant from the ROI size (the ROI including joint space exhibiting better precision results than ROI including solely the subchondral plate). For a constant size of the ROI, the precision results were site-dependant. Inter-observer RMS CV results ranged from 0.59 to 5.01% according to ROI and software used. For the specific task of monitoring medial sBMD in the ROI including solely subchondral plate, forearm flexion condition produced the highest intra-observer and short-term precision (respectively RMS CV: 0.45% and 2.77%; LSC: 0.013 and 0.080 g/cm(2)). CONCLUSION: Taking account into the excellent precision of the sBMD measurements expressed as RMS CV with the protocol proposed in the present study, clinical application of these measurements might be envisaged.

Effects of deltamethrin (pyrethroid insecticide) on growth, reproduction, embryonic development and sex differentiation in two strains of Daphnia magna (Crustacea, Cladocera).

Acute and different chronic ecotoxic effects of deltamethrin have been investigated on two strains (coming from two different laboratories) of Daphnia magna. The effective concentrations immobilizing 50% of daphnids (EC50s) after 24 h and 48 h were 9.40 and 0.32 µg L(-1), 8.86 and 0.63 µg L(-1) for first strain (strain 1) and second strain (strain 2), respectively. Thus, there was an increase of deltamethrin ecotoxicity with time of exposure as confirmed by chronic studies. After 21 days of exposure to deltamethrin, daphnids have showed significant effects on survival at deltamethrin concentrations of 0.16 µg L(-1) and 0.31 µg L(-1) for strains 1 and 2, respectively. Eleven other endpoints were examined: body length, population growth rate and various reproductive parameters (days to first brood, number of broods, number of cumulative molts and number of neonates), embryotoxicity and appearance of males. IC10 values related to the number of juveniles per live adult were 11 and 46 ng L(-1) for strains 1 and 2, respectively. Furthermore, an increase in embryo deformities was observed at the highest concentrations tested for both strains. Following deltamethrin exposure, undeveloped second antennae, curved or unextended shell spines, and curved post abdomen spines were observed in live neonates. The production of male juveniles was only registered with strain 1 at 0.16 µg L(-1). Results suggest that deltamethrin could act as an endocrine disruptor in D. magna as it interferes with sex determination and development abnormality but there is a difference in sensitivity between the two tested strains.

The role of muscle strength & activation patterns in patellofemoral pain.

BACKGROUND: To investigate the extent to which quadriceps muscle activation and strength are responsible for patellofemoral pain. METHODS: A pain on-off switch system synchronized with a force transducer and surface electromyography was utilized on 32 volunteer patellofemoral pain patients during maximal isometric and squat exercises. FINDINGS: There were 26 patients out of the 32 tested who complained of pain during the squat or isometric test, of these 20 subjects presented a significant advantage for the vastus lateralis compared to the vastus medialis obliquis activation and 12 patients had decreased quadriceps strength of the symptomatic compared to the non symptomatic leg. All patients who demonstrated weak vastus medialis obliquis activation during the isometric exercise possessed the same symptoms during the squat. On the other hand, 9 patients who showed diminished vastus medialis obliquis activation during the squat displayed equal activation between the vastus medialis obliquis and the vastus lateralis during the isometric task. With regard to the timing for the onset of muscle activation, there were only 4 patients who had a difference (P=0.03) between the symptomatic (0.042 s) and non-symptomatic legs (0.011 s). INTERPRETATION: Causes for patellofemoral pain vary and are not necessarily a result of quadriceps strength deficit or vastus medialis obliquis activation weakness. Patellofemoral pain patients who possess lower vastus medialis obliquis activation compared to the vastus lateralis do not necessarily have quadriceps weakness while patients presenting with quadriceps strength deficits do not always have an imbalance between vastus medialis obliquis and vastus lateralis activation.

Improvements of Adaptive Filtering by Optimal Projection to filter different artifact types on long duration EEG recordings.

Adaptive Filtering by Optimal Projection (AFOP) is an automatic method for reducing ocular and muscular artifacts on electro-encephalographic (EEG) recordings. This paper presents two additions to this method: an improvement of the stability of ocular artifact filtering and an adaptation of the method for filtering electrode artifacts. With these improvements, it is possible to reduce almost all the current types of artifacts, while preserving brain signals, particularly those characterising epilepsy. This generalised method consists of dividing the signal into several time-frequency windows, and in applying different spatial filters to each. Two steps are required to define one of these spatial filters: the first step consists of defining artifact spatial projection using the Common Spatial Pattern (CSP) method and the second consists of defining EEG spatial projection via regression. For this second step, a progressive orthogonalisation process is proposed to improve stability. This method has been tested on long-duration EEG recordings of epileptic patients. A neurologist quantified the ratio of removed artifacts and the ratio of preserved EEG. Among the 330 artifacted pages used for evaluation, readability was judged better for 78% of pages, equal for 20% of pages, and worse for 2%. Artifact amplitudes were reduced by 80% on average. At the same time, brain sources were preserved in amplitude from 70% to 95% depending on the type of waves (alpha, theta, delta, spikes, etc.). A blind comparison with manual Independent Component Analysis (ICA) was also realised. The results show that this method is competitive and useful for routine clinical practice.

Lipid peroxidation in judoists using oral contraceptives.

12 female judoists using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone for 20 ± 12 months (mean ± SD) were compared with a control group of 14 judoist noncontraceptive users (NCU) in order to evaluate resting (T1) and postexercise (T2) lipid peroxidation (LPO) and antioxidant parameters. Data were collected 20 min before and 10 min after a morning session of judo training and included determination of lag phase (Lp) before free radical-induced oxidation, glutathione peroxidase (GPx), α-tocopherol, retinol, and oxidative stress markers related to LPO. Significantly higher resting oxidative stress (+125.8 and +165.2% for malondialdehyde and lipid peroxides, respectively) and lower values of Lp and GPx (-23.4 and -12.1%, respectively) were observed in the OCU compared with NCU. The judo training session induced an increase in plasma LPO whatever the treatment. We noted significant increases in Lp (+14.7%; p<0.05 vs. preexercise) and GPx (22.1%; p<0.05 vs. preexercise) only in the NCU group. We suggest that a judo training session favourably altered some antioxidants in NCU but not in OCU. As excessive oxidative stress is linked to the development of several chronic diseases, the use of agents to reduce antioxidants may be reasonable in OCU.

Back pain during pregnancy and living conditions: a comparison between Beninese and Canadian women.

OBJECTIVE: The objective of this exploratory study was to investigate and underline the contrasts between African and Canadian pregnant women, and their living conditions. We also intended to evaluate how they compared on low back pain, a condition that seems common across all pregnant women everywhere in the world. SUBJECTS AND METHOD: Thirty Beninese and 50 Canadian women were surveyed with demographic disability questionnaires O.D.I at approximately 25 weeks of pregnancy. RESULTS: There were large differences between the two groups due to the differences between the life style. Beninese women were more likely to be self-employed or housewives, while Canadian women were more likely to be employed. Beninese women worked for 18hours more per week, and had on average one more child at home. A higher percentage of Beninese women reported back pain, 83% versus 58% for Canadian women, but the disability scores were in the "moderate disability" range for both groups. A higher percentage of Beninese women also reported at least severe disability, 33% versus 14% for Canadian women. CONCLUSION: The results suggest that the higher percentages of Beninese women affected by back pain and by severe back pain is related to the longer hours worked and more strenuous physical work performed.

Evidence for a distinctive pattern of bone formation in enthesophytes.

OBJECTIVES: The mechanism of new bone formation at entheses in spondyloarthritis (SpA) is poorly understood, but it is a key factor contributing to disability in disease. As bony spur development is also an age-related phenomenon, spurs in elderly dissecting room cadavers were studied in order to establish general principles relating to their development. METHODS: Spurs of different sizes were studied by routine histology at 26 different entheses (a total of 76 specimens) from the upper limb, lower limb and spine. The percentage of bone:marrow was compared in the posterior part of the calcaneus in cadavers with and without Achilles spurs to ascertain the relationship between spurs and immediately adjacent trabecular bone. RESULTS: Bony spur formation was a common age related phenomena and typically occurred in the most fibrous part of an enthesis. Paradoxically, it was often heralded by the initial appearance of a thick zone of calcified fibrocartilage that subsequently developed bony nodules within it. Uncalcified fibrocartilage was more prominent around large spurs. Endochondral, intramembranous and chondroidal ossification all contributed to spur formation and growth, but cell hypertrophy and florid vascular invasion of a cellular calcified cartilage, typical of endochondral ossification, were not conspicuous features. CONCLUSION: Entheseal new bone formation occurs by a combination of three methods of ossification. However, endochondral ossification was atypical and differed from that seen in the normal development of cartilage bones or during fracture healing. How the inflammatory process modulates these processes could lead to a better understanding of entheseal new bone formation in SpA.

The relationship between the extensor tendon enthesis and the nail in distal interphalangeal joint disease in psoriatic arthritis--a high-resolution MRI and histological study.

OBJECTIVES: Diffuse swelling of the distal interphalangeal (DIP) joint beyond the joint margin is a common feature of arthritis in psoriatic arthritis (PsA). The purpose of this study was to explore the microanatomical basis for the inflammation and nail disease in PsA using a combined high-resolution magnetic resonance imaging (MRI) and histological studies. METHODS: High-resolution MRIs of the DIP joint were obtained in 30 subjects [10 PsA, 10 osteoarthritis (OA) and 10 normal volunteers]. The relationship between the DIP joint capsule and associated tendon enthesis and the nail bed and root were evaluated. Histological studies to define the relationship between the normal cadaveric DIP joint capsule and the nail root were performed on the middle and ring fingers of 10 dissecting room cadavers. RESULTS: On MRI, the dorsal capsular enthesis was the epicentre of an inflammatory reaction. This extended to involve the soft tissues adjacent to the nail in 8 of 10 cases in PsA, but only 4 of 10 cases in OA where the inflammation is less intense and in none of the normal fingers. The DIP joint capsule was intimately linked with the nail complex on histology, with the dorsal, volar and lateral aspects of the nail bed being ensheathed in fibres extending from the entheses. CONCLUSION: The study suggests that the extended nature of the enthesis organ associated with the DIP joint may explain the diffuse nature of the inflammatory response around the nail in PsA. Therefore the nail is as much an integral part of the enthesis organ as it is of the skin, which has implications for a better understanding of the disease.

Microdamage and altered vascularity at the enthesis-bone interface provides an anatomic explanation for bone involvement in the HLA-B27-associated spondylarthritides and allied disorders.

OBJECTIVE: To describe the basis for entheseal-associated bone disease in the spondylarthritides, by analyzing microanatomic and histopathologic relationships between soft tissue, bone cortex, and adjacent trabeculae. METHODS: Serial sections from 52 entheses were examined; these entheses encompassed small and large insertions in the upper limb (n = 21), lower limb (n = 27), and spine (n = 4) from 60 cadavers. Enthesis microdamage (fissuring) as well as vascular and reparative changes were evaluated. Contact radiographs were used to ascertain the relationship between entheses and the trabecular network. RESULTS: At virtually all fibrocartilaginous entheses, the deep cortical boundary was extremely thin (typically 50-600 microm) or indistinguishable, and 96% of entheses had small holes in the cortical shell (typically 100-400 microm wide). Such regions were frequent sites of bone formation and renewal (96%) and microdamage (31%); these changes were more common in the lower limb. The presence of blood vessels near holes in the cortical shell was common; in 85% of attachments, blood vessels were present on the soft tissue side of the enthesis. Highly orientated trabeculae were more obvious in the lower limb than the upper limb (59% versus 29%). CONCLUSION: The trabecular network supporting the cortical shell is an integral part of the enthesis, transferring load to an extensive skeletal region. In many cases, tendons/ligaments are anchored directly to such networks. This functional integration is associated with microdamage and repair at the hard tissue-soft tissue interface. These findings have implications for understanding bone involvement in SpA and for the SpA concept in general, especially the hypothesis that enthesis-bone architecture may be important in disease initiation.